Dietary saturated fats are implicated as a major risk
factor in hypercholesterolaemia and cardiovascular disease. Palm
oil is a major source of the world's supply of oils and fats, but
because of its relatively high content of saturated fatty acids
(principally palmitic acid), its consumption has come under
intense scrutiny over the last decade owing to potential health
implications. Based on studies carried out more than thirty years
ago, the hypothesis was developed that lauric, myristic, and
palmitic acid were the three principal cholesterol-raising
saturated fatty acids. Since palmitic acid is the most abundant
fatty acid in the diet, the cholesterol-raising effect of all
saturated fatty acids was accordingly assigned to it. However,
recent studies from both humans and experimental animals suggest
that not all saturated fatty acids are cholesterol-raising. When
all dietary fatty acids are equalized, with the exception of the
two being tested, palmitic acid appears to have no impact on the
plasma cholesterol in normocholesterolaemic subjects when dietary
cholesterol intake is below a certain critical level (400 mg per
day). Only when cholesterol consumption exceeds this level, or
when hypercholesterolaemic subjects are studied, does palmitic
acid appear to increase the plasma cholesterol. These
differential effects of palmitic acid on plasma cholesterol are
thought to reflect differences in LDL-receptor status.
Collectively these data imply that, for most of the world's
population, palm oil would be an inexpensive and readily
metabolized source of dietary energy with minimal impact on
cholesterol metabolism.

Introduction

A substantial body of data implicates dietary saturated fat as
one of the risk factors in hypercholesterolaemia and
cardiovascular disease [1, 2]. However, the debate over what
constitutes the "ideal" fat and, more specifically, its
fatty acid profile has generated much controversy and confusion
among both scientists and laymen. The subject is complicated
further by economics. Since dietary fat is derived invariably
from the consumption of various oils and meat and dairy products,
advice from the scientific community affects production and
distribution trends, and, in certain instances, specific national
interests.

Palm oil is a major contributor to the world's supply of fats
and oils and is arguably the most cost-effective source of edible
fat. Because it has a relatively high content of saturated fatty
acids compared with most other oils, the principal one being
palmitic acid, the growing presence of palm oil in the world
market-place has been the focus of much discussion over the last
decade. Although palm oil (with other so-called tropical oils)
has typically represented less than 3% of the total fat consumed
in the United States, it is a major source of dietary fat in
Latin American, South-East Asia, China, India and Pakistan, parts
of West Asia, and Africa. Thus, emerging evidence on its
metabolic impact based on carefully constructed scientific
studies both in animals and in clinical settings will have
far-reaching consequences affecting two-thirds of the world
population. Due in part to palm oil's potential as a
cost-effective source of fat in human nutrition, the scientific
community must guard against intentional or unintentional bias
and maintain a responsible perspective when reporting its
findings or making recommendations concerning consumption of the
oil.

It is apparent from recent data on lipoprotein metabolism in
humans and animals that focusing on specific fat classes
(saturated, mono-unsaturated, polyunsaturated) is
a gross over simplification of the effect of dietary fat on
cholesterol metabolism, including plasma lipoproteins. Even a
superficial analysis of some of the so-called saturated
fats (e.g., palm oil, lard, tallow, butter, coconut oil) reveals
that they have distinct profiles (table 1) and empirically exert
different metabolic effects. Accordingly, research in recent
years has shifted toward elucidating the effects of specific
dietary fatty acids in triglycerides, as opposed to specific
classes of fats, on plasma lipids and lipoprotein metabolism.
Detailed reviews on palm oil per se have been published recently
[3-5]. Our purpose is to summarize the current knowledge
concerning its impact on lipid metabolism from the perspective of
its fatty acid profile.

Both RDB and red palm oils have fatty acid
compositions similar to that of crude palm oil.

Dietary fats and serum cholesterol

Cardiovascular disease accounts for almost half
a million deaths annually in the United States. One of the most
easily measured indicators of risk is the serum or plasma
cholesterol concentration, specifically the level of low-density
lipoprotein (LDL) cholesterol, called the "bad"
cholesterol. An elevated level of LDL cholesterol is a major risk
factor. Conversely, an elevated level of high-density lipoprotein
(HDL) cholesterol (the "good" cholesterol) is believed
to confer protection. Hence, in any individual with elevated
cholesterol, the primary goal is to lower the LDL cholesterol
level to reduce the risk of cardiovascular disease. Although this
objective may be achieved by drug therapy, one of the first
interventions is dietary modification. Since 1908 we have known
that diet affects serum cholesterol levels and, in the case of
laboratory animals, the ability to develop atherosclerosis [6].
Although numerous dietary factors have been implicated on the
basis of epidemiological studies, the single most important
variable that has come under the most scrutiny is fat.

Saturated, mono-unsaturated, and
polyunsaturated fats

Classification of fats has typically been based
on their constituent fatty acids. Hence, fats in which the fatty
acids with no double bonds (those most frequently encountered are
1218°C, lauric, myristic, palmitic, and stearic respectively)
represent more than 50% of the total fatty acids are referred to
as saturated; those in which the majority of total fatty acids
have one double bond (usually oleic acid) are designated
mono-unsaturated; and those in which fatty acids with two or more
double bonds are the majority (usually linoleic acid) are
referred to as polyunsaturated. Therefore, although two different
fats may both be referred to as saturated, they may have
distinctly different fatty acid profiles-for example, coconut
oil, rich in lauric and myristic acid; palm oil, rich in palmitic
acid; and cocoa butter, rich in stearic acid. The two most
abundant fatty acids in nature are oleic and palmitic, which
raises serious doubts that either would be considered detrimental
to normal metabolic processes.

Since the 1950s numerous studies both in humans
and in animals have investigated the effects of dietary fat
saturation on cholesterolaemia [1, 2, 7-11]. The human studies
were complicated by numerous variables, including the age and sex
of the subjects, whether they were carried out in a metabolic
ward or had free-living subjects, whether the subjects consumed
liquid-formula diets or solid diets, and so on. The general
consensus emerged, however, that saturated fats were twice as
effective in elevating serum cholesterol as polyunsaturated fats
were in lowering it. Mono-unsaturated fats were considered
neutral (i.e., as having no effect on serum cholesterol). These
observations led to a massive introduction of polyunsaturated
fats in the marketplace from the 1950s, which doubled the typical
polyunsaturated consumption between 1940 and 1985 from 2.5% to
5.5% of energy (en%) [12]. This rise in intake was associated
with a peak in serum cholesterol and a decline in coronary heart
disease [1].

Regression equations

Two independent research groups [8, 10]
translated these early results into mathematical regression
equations that have been used to predict the average change in
serum cholesterol that might be expected for a given change in
the percentage of energy consumed from a specific class of fatty
acids. In addition, the equations included a
cholesterol-elevating contribution from dietary cholesterol
itself. These early studies also assigned essentially equal
cholesterol-raising power to three saturated fatty acids, 12:0,
14:0, and 16:0, whereas the saturated fatty acids 10:0 and 18:0
were considered neutral. Even though an initial study and
regression analysis showed myristic acid (14:0) to be four times
as potent as palmitic acid (16:0) in raising serum cholesterol
[5], a subsequent study with modified (transesterified) fat led
to a revised opinion and to the labelling of 12:0, 14:0, and 16:0
saturated fatty acids as equivalent [13]. The fact that palmitic
acid is the most abundant fatty acid in the food supply has meant
that the cholesterol-raising property of all saturated fats has
generally been attributed to their palmitic acid content. By the
same argument, because myristic acid (and lauric acid) typically
represent less than 2% of the energy in the American diet, their
cholesterol-raising potential has been overlooked or dismissed as
having any impact of consequence.

These studies focused on types of fats and
oils, from which inferences were made about fatty acids and their
ability to raise and lower serum cholesterol. We now have
substantially more information about lipoprotein metabolism. This
is important because the LDL:HDL ratio appears to be critical to
the atherogenic potential of the lipoproteins. In theory it is
conceivable that a proper balance in the fats (i.e., fatty acids)
consumed will greatly enhance the circulating lipoprotein
profile. In addition, the discovery of the LDL receptor [14]
revealed a complex metabolic pathway that must be appreciated to
understand fully the impact that dietary fatty acids have on
lipoprotein metabolism. Although regression equations [9,10] have
proved useful in attempts to sort out the saturated and
unsaturated fatty acid effects on serum cholesterol among
populations, they provide minimal information on how dietary fat
effects lipoprotein metabolism, especially as it pertains to
individuals. Also, it is now apparent that over the full range of
potential 18:2 intakes (1-30 en %) the resulting decrease in
plasma cholesterol may be non-linear.

Is mono-unsaturated fat as good as
polyunsaturated fat?

In recent years a series of reports have
suggested that the cholesterol-lowering potential of
mono-unsaturated fat compares favourably with that of
polyunsaturates, lowering LDL without lowering HDL [15,16]. This
claim is surprising in light of data indicating that
monounsaturated fatty acids are relatively neutral. We believe
that total substitution with a mono-unsaturated fat in the
experimental settings (which seldom occurs in Western diets
because other fatty acids are present) does two important things:
it potentially removes all the myristic acid from the diet, and
it supplies more than enough 18:2 (about 4 en%) to maximize the
LDL-receptor efficiency in the absence of 14:0 [16]. Our data
suggest that 18:1 is not as effective as 18:2 when either 14:0 or
cholesterol has down-regulated the receptors at a fatty acid
intake below this critical 18:2 threshold.

In addition, on the basis of the above premise
and as discussed previously [17, 18], it follows that any data
obtained with a ratio of dietary polyunsaturated to saturated fat
outside the normal range in the human diet (0.2-1.0) is likely to
generate spurious results for the reasons stated. That is why
feeding all the fat as safflower oil or coconut oil is not a
legitimate, practical, or clinically meaningful evaluation of a
saturated or polyunsaturated fat effect. Clearly, to derive valid
information about the physiological impact of dietary fat, and
specifically fatty acids, it should be fed at the levels that the
body normally encounters.

Is palmitic acid cholesterol-elevating?

In an initial study with three different
species of monkeys [19], tallow and lard (as saturated fats) were
not much more cholesterolaemic than corn oil (a polyunsaturated
fat) and were less so than other saturated fats, coconut oil or
butter, even though both lard and tallow contain appreciable
amounts of saturated fatty acids. Analysis revealed distinctly
different profiles of the saturated fatty acids. This prompted us
to question the generally held belief that the 12-16°C fatty
acids were equivalent in terms of their cholesterol-raising
ability. On further investigation with diets using blends of oils
in which total saturated, mono-unsaturated, and polyunsaturated
fatty acids were held constant, the exchange of dietary 16:0 for
12:0 + 14:0 [20] caused a decrease in the plasma cholesterol
(table 2). This result clearly suggested that palmitic acid was
not cholesterolaemic but neutral under those conditions, and that
the widely held belief that all saturated fatty acids are the
same was invalid. In a collaborative study, the same result was
obtained in normocholesterolaemic humans, even with 300 mg of
cholesterol in the diet [21]. Essentially similar results were
obtained for hamsters fed blends of fats to control for specific
fatty acids. Furthermore, the HDL cholesterol and the mRNA
abundance for the LDL receptor were increased by 16:0 [22].

TABLE 2. Effect of exchanging 16:0 for
12:0 + 14:0 on lipid values in 21 monkeys of three species fed
cholesterol-free purified

Fatty acid (% of
total)

Cholesterol (mg/dl
plasma)

Diet

12:0

14:0

16:0

Total

LDL

HDL

LDL: HDL

A

23.8

9.6

8.6

205 ± 11*

92 ± 8*

99 ± 4*

0.95 ± 0.08

B

13.4

5.8

25.1

203 ± 10

87 ±7

96 ± 6

0.98 ± 0.09

C

0.2

1.0

40.3

183 ± 9*

79 ± 6*

86 ± 6*

0.89 ± 0.07

Adapted from ret 20.

Diets were formulated to give identical levels
of total saturated, mono-unsaturated, and polyunsaturated fatty
acids, with 16:0 increased at the expense of 12:0 + 14:0 in going
from diet A to C.

Values are mean ± SEM.

* Means in the same column sharing an asterisk
are significantly different.

In a subsequent study [23], monkeys were fed
diets rich in either 12:0 + 14:0 or 16:0 + 18:1 and
simultaneously injected with homologous 125I-VLDL and 131I-LDL
to assess apo B (and therefore very low-density lipoprotein
[VLDL] and LDL) metabolism. Analysis of apo B specific activity
data showed that monkeys fed the 16:0 + 18:1-rich diet had
increases in the pool size of VLDL apo B and its transport rate
and decreases in the pool size of LDL apo B and its total
transport rate. The irreversible fractionated catabolic rate
(FCR) for VLDL apo B and LDL apo B was similar between dietary
groups (table 3). Although the total apo B and VLDL apo B
transport rates were increased, LDL apo B concentration was
reduced because of a decrease in the mass and proportion of LDL
apo B derived independently of VLDL catabolism. This study
further suggested that 16:0 is unlike 12:0 or 14:0, and clearly
indicated that saturation of dietary fat has distinct effects on
the transport of LDL apo B from VLDL-dependent and -independent
pathways.

These studies [20, 22, 23] used
cholesterol-free diets and normocholesterolaemic animals, and the
results suggested that 12:0 + 14:0 is more cholesterolaemic than
16:0, and that 16:0 and 18:1 are neutral in terms of their
effects on plasma cholesterol, as originally suggested [9]. A
reappraisal of the literature, especially reports that developed
the notion that palmitic acid was a cholesterol-elevating fatty
acid, revealed two telling points. First, most studies used
patients with mild (>220 mg/dl) to severe (>250 mg/dl)
hypercholesterolaemia [9, 15], and many employed a design in
which fat was fed in a background of dietary cholesterol. Thus,
studies in both hypercholesterolaemic human subjects [15] and
non-human primates fed cholesterol-containing diets [24]
suggested 16:0 was hypercholesterolaemic compared with 18:1.

In both these situations some degree of
down-regulation of the LDL receptor would be expected [14]. Since
the LDL receptor, in addition to clearing circulating LDL, is
responsible for clearing VLDL remnants [2, 25], when its activity
is compromised it will fail to clear VLDL remnants. Consequently,
the latter would be further metabolized to lead to an expanded
LDL pool. However, when LDL receptor activity is not compromised
by cholesterol feeding or other environmental-genetic
interactions, as in our rhesus study [23], no expansion of the
LDL pool occurs, since VLDL remnants are effectively removed to
preclude their conversion to LDL. As a consequence, no elevation
in plasma cholesterol was apparent when 16:0 was fed [19, 20, 22,
23].

As a working hypothesis, we suspected that in
cases of normal LDL-receptor activity (i.e., in the absence of
dietary cholesterol), 16:0 and 18:1 would exert similar effects
on receptor-mediated LDL clearance. To test this,
normocholesterolaemic cebus monkeys fed diets rich in 16:0,18:1,
or 18:2 without cholesterol, were coinjected with radiolabelled
native and methylated LDL (table 4). Receptor-mediated LDL
clearance was similar for all three diets [26]. The total
cholesterol was lower in cebus fed the 18:2-rich diet, but this
was totally attributable to decreased HDL. The LDL concentrations
and clearance were similar for all three diets. In fact, the
16:0-rich diet produced the lowest LDL:HDL ratio, significantly
better than 18:2-rich diet, supporting our previous finding in
hamsters [22] that 16:0 may be the saturated fatty acid
responsible for the rise in HDL associated with saturated fat
consumption. On the basis of our cebus data [26], we exchanged
16:0 for 18:1 in normocholesterolaemic humans (7 en%) and again
observed no differences in LDL or HDL or total cholesterol,
whereas increasing 12:0 + 14:0 caused a significant rise in LDL
and total cholesterol [27], just as in our earlier monkey study
[20].

Values are the mean ± SD of nine monkeys per
dietary group. Figures in parentheses represent the percentage of
the total FCR that is attributable to non-receptor- or
receptor-mediated pathways.

Using accumulated data from the feeding of 16
different cholesterol-free fat blends, we generated regression
equations (of the type originally developed by Hegsted) for the
fatty acid impact on the plasma cholesterol response in our cebus
monkeys [28]. The dietary 14:0 and 18:2 intakes alone were able
to explain almost 92% of the observed variation in plasma
cholesterol, with 16:0 and 18:1 appearing to be neutral. In view
of our working hypothesis concerning the importance of the LDL
receptor, we decided to re-examine the report in which the entire
dietary fatty acid profile (not just saturated versus
polyunsaturated) was published together with the cholesterol
response in a large number of dietary manipulations (36 diets)
using the same people [9]. Just as originally reported for all 36
diets, we found that 14:0 was four times as cholesterolaemic as
16:0, with 18:2 the only fatty acid that lowered cholesterol.
However, based on our hypothesis that 16:0 was neutral when
LDL-receptor activity was not compromised (e.g., by dietary
cholesterol), we analysed the data at low (<= 300 mg) or high
(>400 mg) cholesterol intakes. In the 17 human diets in which
cholesterol intake was 300 mg or less, 85% of the observed
variation in serum cholesterol could be explained solely on the
basis of 14:0 and 18:2. However, in the 19 human diets containing
more than 400 mg cholesterol, 16:0 appeared slightly
cholesterolaemic. We now also have accumulated data from
normocholesterolaemic gerbils fed a total of 33 cholesterol-free
diets [29]. Again, 14 0 and 18:2 explain almost 90% of the
observed variation in plasma cholesterol. Including dietary 16:0
and 18:1 in the regression failed to improve the predictability
of the regression on the cholesterol response.

As an additional test of our hypothesis, we
recently fed normocholesterolaemic cebus monkeys cholesterol-free
diets rich in 16:0, 18:1, or equivalent amounts of 16:0 + 18:1.
Again, no differences were noted in plasma lipid or LDL and HDL
kinetic values among the groups [30]. Only when LDL receptors
were down-regulated with dietary cholesterol (0.3% w/w) was a
hypercholesterolaemic effect of 16:0 apparent (authors' personal
observation), similar to the observations of others in monkeys
fed similar diets [24].

Summary

Palmitic acid is best considered a transitional
fatty acid; no apparent abnormality in cholesterol metabolism
develops when energy flow is normal and fat is transported and
cleared under normal physiological circumstances. Circumstances
may develop, however, as in hypercholesterolaemic persons,
wherein lipoprotein production or clearance becomes impaired,
such as obesity and hyperinsulinaemia where compromised
LDL-receptor activity is a factor. In such individuals palmitic
acid may add to the cholesterolaemia because it represents the
primary stimulus for fat transport as triglycerides among the
fatty acids, thereby contributing to the pool of lipoproteins
that must subsequently be subjected to an impaired clearance
process. Only then does 16:0 appear to have a negative impact on
cholesterol metabolism [31, 32]. The inference is that for most
of the world's population, in whom adequate energy consumption
and not energy storage (adiposity) is the problem, palm oil
represents an ideal, inexpensive, highly palatable source of
energy in the food supply.

References

1. Committee on Diet and Health, Food and
Nutrition Board, Commission on Life Sciences, National Research
Council. Fats and other lipids. In: Diet and health: implications
for reducing chronic disease risk. Washington, DC: National
Academy Press, 1989:159258.